Understanding and Anticipating Therapeutic and ADverse Responses in Anti-cancer Immune Checkpoint Inhibition Towards a Better Therapeutic Management of Patients

NCT ID: NCT05973344

Last Updated: 2026-02-04

Basic Information

• Recruitment Status: RECRUITING
• Total Enrollment: 200 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2024-02-09
• Study Completion Date: 2030-02-09

Brief Summary

The goal of this observational study is to explore the value of blood biomarkers for the purpose of predicting irAE development in cancer patients treated with immune checkpoint inihibitors (ICI) alone or in combination with other treatments (chemotherapy, radiotherapy and targeted therapy).

Data and blood samples will be collected from participants at different time points as part of routine follow-up visits. Data and blood samples will be analysed. Analysis will include the characterization of immune cells by mass and flow cytometry.

Detailed Description

Advances in treating patients with immunotherapy have dramatically changed cancer morbidity and mortality. Immune checkpoint inhibitors (ICI), alone or combined with other treatments, are currently used both as standard of care or in experimental settings for various cancers. ICI treatment induces objective clinical responses in 20-40% of patients (varies by tumor type); however, this leaves a majority of patients that do not respond to ICI therapy. ICI drugs purposely release immune regulatory controls and consequently increase immune activities; however, this release also provokes a significant risk of immunerelated adverse events (irAEs) such as dermatitis, hepatitis, thyroiditis and colitis, and less frequently but clinically important, hypophysitis, myocarditis and pneumonia. While the incidence of irAE is highly variable and influenced by many factors, Phase I and II trials reported rates from 10% to 80% for any grade irAE while an irAE of grade 3 or higher was observed in 2.5% to 18% of subjects. Recently, Jing et al. demonstrated that 20% of patients receiving anti-PD-1/PD-L1 had at least one irAE by integrating real-world pharmacovigilance of 26 tumor types for a total of 18,706 patients. Presently, the specific immune mechanism(s) driving irAE are unknown and biomarkers that predict their onset, particularly high-grade irAE, are urgently needed. For this reason, we hypothesize that an in-depth characterization and comparisons of the cell subpopulations composing and interacting within the primary cancer lesions, the peripheral blood, and in the organs in which irAE arise could help to better understand but also predict the clinical therapeutic response or/and irAE in patients with advanced cancers treated with ICI.

The research is a non-interventional monocentric prospective study of humans for the development of biological and medical knowledge, in which the procedures are performed and the products used in the usual manner, without additional or unusual diagnostic, treatment or monitoring procedures. The study includes patients monitored for their cancer at CHU of Brest and treated using Immune Checkpoint Inhibitors. Data and peripheral blood (47mL) will be collected at different time points as part of routine follow-up visits for analysis. Analysis will include the characterization of immune cells by mass and flow cytometry.

Conditions

Cancer

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Eligibility Criteria

Inclusion Criteria

• Adequate bone marrow function as defined below

• Absolute neutrophil count ≥ 1500/µL or 1.5x109/L
• Hemoglobin ≥ 9 g/dL
• Platelets ≥ 100000/µL or 100x109/L
• Adequate liver function as defined below

• Serum total bilirubin ≤ 1.5 x ULN. In case of known Gilbert's syndrome < 3xUNL is allowed
• AST (SGOT)/ALT (SGPT) ≤ 3.0 x ULN
• Alkaline phosphatase ≤ 3.3 x ULN
• Adequate renal function as defined below

_- Creatinine ≤ 1.5 x UNL or creatinine clearance > 60 mL/min

• Patient monitored for their cancer at CHU of Brest
• Did not oppose for their samples and clinical data to be used for translational research
• Non-opposition form obtained prior to any study related procedure

Exclusion Criteria

• Patient with a significant medical, neuro-psychiatric, or surgical condition, currently uncontrolled by treatment, which, in the principal investigator's opinion, may interfere with completion of the study
• Patient already receiving ICI
• Primary immunodeficiency and/or history of allogenic transplantation
• Current active infection
• Known Human Immunodeficiency Virus (HIV), Hepatitis B Virus (HBV), or Hepatitis C Virus (HCV) infection (with the exception of chronic or cleared HBV and HCV infection)
• Subject of guardianship (tutorship, curatorship)
• Active pregnancy

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University Hospital, Brest

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Benjamin Auberger

Role: PRINCIPAL_INVESTIGATOR

CHU Brest

Locations

Brest University Hospital

Brest, , France

Site Status: RECRUITING

Countries

France

Central Contacts

Benjamin Auberger

Role: CONTACT

benjamin.auberger@chu-brest.fr

+33298223740

Facility Contacts

Benjamin Auberger

Role: primary

Other Identifiers

2022-A02237-36

Identifier Type: OTHER

Identifier Source: secondary_id

29BRC22.0189 (TADIG-P)

Identifier Type: -

Identifier Source: org_study_id